Response: We’re proud and excited to make Rebinyn® (Coagulation Factor IX (Recombinant), GlycoPEGylated) available as a new extended half-life treatment for hemophilia B management.

Rebinyn® is an injectable medicine used to treat and control bleeding in adults and children with hemophilia B. It can be used to treat bleeds when they occur and to manage bleeding during surgery. Rebinyn® is not used for routine prophylaxis or for immune tolerance induction in patients with hemophilia B.

Hemophilia B is a serious, chronic, inherited bleeding disease that affects about 5,000 people in the U.S. People living with hemophilia B have low levels of clotting Factor IX protein in the blood, often resulting in prolonged or spontaneous bleeding, especially into the muscles, joints or internal organs.Continue reading →

Response: Congenital plasminogen deficiency is a rare genetic disorder that is caused by mutations in the PLG gene. Mutations in this gene lead to clinical manifestations such as fibrinous deposits on mucous membranes leading to disruption of tissue or organ function. These symptoms, when untreated, lead to significant morbidity and decreased quality of life. Life-threatening episodes may occur especially when the respiratory system is affected. There is currently no established approach to treatment of type 1 plasminogen deficiency and the available topical and systemic therapies (e.g. FFP, corticosteroids, immunomodulatory drugs, anticoagulants, amongst others) lack consistent efficacy. Patients may undergo multiple surgeries to remove lesions, but this approach typically leads to regrowth of lesions. Prometic’s intravenous plasminogen replacement therapy represents the first direct treatment for this serious disorder.

Response: The new IDELVION results presented at the American Society of Hematology (ASH) are from a pooled analysis of clinical studies from the global PROLONG-9FP clinical development program. The analysis assessed the relationship between estimated factor IX activity levels and clinical bleeding risk in adult hemophilia B patients treated with IDELVION using prophylaxis or on-demand (episodic) treatment.

The PROLONG-9FP clinical development program included five Phase I through Phase III open-label, multicenter studies evaluating the pharmacokinetics, safety and efficacy of IDELVION in children and adults with hemophilia B.

Regarding: Post Hoc Analysis to Evaluate the Effect of Recombinant Factor IX Fc Fusion Protein (rFIXFc) Prophylaxis in Adults and Adolescents with Target Joints and Hemophilia B being presented at the World Federation of Hemophilia (WFH) 2016 World Congress

MedicalResearch.com: What is the background for this study?

Response: People with hemophilia B experience prolonged bleeding episodes that can cause pain, irreversible joint damage and life-threatening hemorrhages. For people with severe hemophilia, most bleeding events occur in joints, with joint damage being the most common complication of the condition.(1) Over time, joints can become severely damaged and an individual can suffer from acute pain as well as restricted range of motion in those joints.(1)

MedicalResearch.com: What are the main findings?

Response: The B-LONG and B-YOND trials evaluated ALPROLIX® [Coagulation Factor IX (Recombinant), Fc Fusion Protein] in hemophilia B patients. In this post-hoc analysis of 37 patients with target joints in B-LONG and B-YOND, most (98.9%) target joints were considered resolved using the International Society on Thrombosis and Haemostasis (ISTH) definition of resolution as ≤ 2 bleeds into the joint within a consecutive 12-month period.

Medical Research: What is the background for this study? What are the main findings?

Dr. Santagostino: Two of our abstracts presented at the 57th ASH Annual Meeting are part of the PROLONG-9FP clinical program evaluating the efficacy and safety of CSL Behring’s investigational long-acting fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP). The first is an oral presentation on results from two Phase III studies and an ongoing extension study of rIX-FP for routine prophylaxis in previously-treated people with hemophilia B.

The two Phase III studies included adolescents and adults (ages 12 to 61) treated with dosing intervals of up to 14 days for 12 to 18 months, and children (ages 1 to 11) who received seven-day prophylaxis treatment for approximately 12 months. Overall, the median annualized spontaneous bleeding rate (AsBR) was 0.00 for all treatment intervals. The extension study is examining longer treatment intervals, including 10- and 14-day intervals in patients younger than 12 and more prolonged treatment intervals in patients older than 18, and so far has reported favorable long-term tolerability with no serious adverse reactions such as the development of inhibitors to factor IX or antibodies to rIX-FP.

A second abstract reported on a surgical sub-study in these trials found that a single pre-operative dose of rIX-FP maintained hemostasis during surgery with responses rated by investigators as “excellent” or “good.” Oven a 14-day perioperative period, patients needed six or seven infusions, and none developed inhibitors to factor IX or antibodies to rIX-FP.

Response: Hemophilia A is an X-linked genetic disorder caused by mutations in the F8 gene, which encodes the blood coagulation factor VIII. Almost half of all severe hemophilia A cases result from two gross (140-kbp or 600-kbp) chromosomal inversions. We derived induced pluripotent stem cells (iPSCs) from patients with these inversion genotypes and used CRISPR-Cas9 nucleases to revert these chromosomal segments back to the WT situation.

Medical Research: What are the main findings?

Response: We isolated inversion-corrected iPSCs with frequencies of up to 6.7% without detectable off-target mutations based on whole-genome sequencing or targeted deep sequencing. Endothelial cells differentiated from corrected iPSCs expressed the F8 gene and functionally rescued factor VIII deficiency in an otherwise lethal mouse model of hemophilia.

Medical Research: What should clinicians and patients take away from your report?

Response: Our results provide a proof of principle for functional correction of large chromosomal inversions in Hemophilia patient-derived induced pluripotent stem cells and suggest potential therapeutic applications in the future.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: We need to prove the safety of patient-derived iPSCs before we move towards clinics.

The safety of iPSCs means to prevent teratoma formation when we do clinical trials.

For that purpose, we need to develop good differentiation protocols into EC cells and to purify the cells as well. In addition, we need much more animal study.

Citation:

Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9

Dong-Wook Kim (2015). Patient-Derived Stem Cells May Be Able To Reverse Hemophilia

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MedicalResearch.com is not a forum for the exchange of personal medical information, advice or the promotion of self-destructive behavior (e.g., eating disorders, suicide). While you may freely discuss your troubles, you should not look to the Website for information or advice on such topics. Instead, we recommend that you talk in person with a trusted medical professional.

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.